<?xml version="1.0" encoding="us-ascii"?><rss version="2.0"><channel><title>NIH OTT RSS Feed - Disease Initiatives - Neglected Diseases</title><link>http://www.ott.nih.gov/rss/default.aspx</link><description>Office of Technology Transfer (OTT).</description><copyright>Copyright 2009 NIH Office of Technology Transfer (OTT). All rights reserved.</copyright><item><title>Chlamydia Vaccine</title><description><![CDATA[Chlamydia trachomatis is an obligate intracellular bacterial pathogen that colonizes and infects oculogenital mucosal surfaces.  The organism exists as multiple serovariants that infect millions of people worldwide.  Ocular infections cause trachoma, a chronic follicular conjunctivitis that results in scarring and blindness.  The World Health Organization estimates that 300?500 million people are afflicted by trachoma, making it the most prevalent form of infectious preventable blindness.  Urogenital infections are the leading cause of bacterial sexually transmitted disease in both industrialized and developing nations.  Moreover, sexually transmitted diseases are risk factors for infertility, the transmission of HIV, and human papilloma virus-induced cervical neoplasia.  Control of C. trachomatis infections is an important public health goal. Unexpectedly, however, aggressive infection control measures based on early detection and antibiotic treatment have resulted in an increase in infection rates, most likely by interfering with natural immunity, a concept suggested by studies performed in experimental infection models.  Effective management of chlamydial disease will likely require the development of an efficacious vaccine. 

This technology claims vaccine compositions that comprise an immunologically effective amount of PmpD protein from C. trachomatis.  Also claimed in the application are methods of immunizing individuals against C. trachomatis.  PmpD is an antigenically stable pan-neutralizing target that, in theory, would provide protection against all human strains, thus allowing the development of a univalent vaccine that is efficacious against both blinding trachoma and sexually transmitted disease.]]></description><link>http://www.ott.nih.gov/Technologies/abstractDetails.aspx?RefNo=1610</link><pubDate>2011-02-28</pubDate></item><item><title>Monoclonal Antibodies Against Dengue and Other Viruses With Deletion in Fc Region</title><description><![CDATA[The four dengue virus (DENV) serotypes (DENV-1 to DENV-4) are the most important arthropod-borne flaviviruses in terms of morbidity and geographic distribution.  Up to 100 million DENV infections occur every year, mostly in tropical and subtropical areas where vector mosquitoes are abundant.  Infection with any of the DENV serotypes may be asymptomatic or may lead to classic dengue fever or more severe dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS), which are increasingly common in the dengue endemic areas.  Immunity to the same virus serotype (homotypic immunity) is life-long, whereas immunity to different serotypes (heterotypic immunity) lasts 2?3 months so that infection with a different serotype virus is possible.  DHF/DSS often occurs in patients with second, heterotypic DENV infections or in infants with maternally transferred dengue immunity.  Severe dengue is a major cause of hospitalization, and fatality rates vary from 

Antibody-dependent enhancement (ADE) has been proposed as an underlying pathogenic mechanism of DHF/DSS.  ADE occurs because preexisting subneutralizing antibodies and the infecting DENV form complexes that bind to Fc receptor-bearing cells, leading to increased virus uptake and replication.  ADE has been repeatedly demonstrated in vitro using dengue immune sera or monoclonal antibodies and cells of monocytic and recently, B lymphocytic lineages bearing Fc receptors.  ADE of DENV-2 infection has also been demonstrated in monkeys infused with a human dengue immune serum. 

We have identified chimpanzee?human chimeric IgG1 mAbs capable of neutralizing or binding to one or more DENV serotypes.  Cross-reactive IgG 1A5 neutralizes DENV-1 and DENV-2 more efficiently than DENV-3 and DENV-4, and type-specific IgG 5H2 neutralizes DENV-4 at a high titer.  Analysis of antigenic variants has localized the IgG 1A5 binding site to the conserved fusion peptide in E.  Thus, IgG 1A5 shares many characteristics with the cross-reactive antibodies detected in flavivirus infections. 

This application claims a variant of an antibody comprising a polypeptide in the Fc region, which binds an Fc gamma receptor (FcgammaR) with lower affinity than the parent antibody.  The variant polypeptide comprises a deletion of nine amino acids at the N-terminus of the CH2 domain in the Fc region.  Introduction of the Fc variant abrogates the antibody-mediated dengue virus replication enhancing activity.  This invention has important implications for the antibody-mediated prevention of dengue virus infection.]]></description><link>http://www.ott.nih.gov/Technologies/abstractDetails.aspx?RefNo=1608</link><pubDate>2011-02-28</pubDate></item><item><title>Development of Dengue Virus Type 3 Vaccine Candidates</title><description><![CDATA[The disease burden associated with dengue virus infection has increased over the past several decades in the tropical and semi-tropical regions of the world, where over 2 billion people live at risk of dengue infection.  Annually, there are an estimated fifty (50) to one hundred (100) million cases of dengue fever, making development of an effective vaccine a priority.  In addition, there is a need for a "travelers vaccine" to protect those visiting dengue virus endemic areas, similar in scope to other currently available "travelers vaccines", such as hepatitis A vaccine. 

The previously identified delta30 attenuating mutation, created in each dengue virus serotype by the removal of 30 homologous nucleotides from the 3'-UTR, is capable of attenuating wild-type strains of dengue virus type 1 (DEN1), type 4 (DEN4) and to a limited extent type 2 (DEN2).  These DEN1delta30 and DEN4delta30 viruses have been shown to be both safe and immunogenic in humans.  However, the delta30 mutation failed to have an attenuating effect on dengue virus type 3 (DEN3).  To generate DEN3 vaccine candidates with a clearly attenuated phenotype, viruses were produced containing 3'-UTR deletions consisting of extensions of the original delta30 mutation or additional mutations which remove stem-loop structures similar to those removed by delta30.  In addition, the entire 3'-UTR of DEN3 was replaced with the 3'-UTR derived from DEN4 and containing the delta30 mutation.  Studies in monkeys demonstrated that these newly developed viruses are highly attenuated, yet sufficiently immunogenic to warrant their further development for use as live attenuated vaccine candidates.  Such viruses are anticipated to become the DEN3 component of a tetravalent vaccine formulation designed to immunize against all four dengue virus serotypes.]]></description><link>http://www.ott.nih.gov/Technologies/abstractDetails.aspx?RefNo=1585</link><pubDate>2011-02-28</pubDate></item><item><title>Dengue Tetravalent Vaccine Containing a Common 30 Nucleotide Deletion in the 3'-UTR of Dengue Types 1, 2, 3, and 4</title><description><![CDATA[The invention relates to a dengue virus tetravalent vaccine containing a common 30-nucleotide deletion (delta30) in the 3'-untranslated region (UTR) of the genome of dengue virus serotypes 1, 2, 3, and 4.  The previously identified delta30 attenuating mutation, created in dengue virus type 4 (DEN4) by the removal of 30 nucleotides from the 3'-UTR, is also capable of attenuating a wild-type strain of dengue virus type 1 (DEN1).  Removal of 30 nucleotides from the DEN1 3'-UTR in a highly conserved region homologous to the DEN4 region encompassing the delta30 mutation yielded a recombinant virus attenuated in rhesus monkeys to a level similar to recombinant virus DEN4delta30.  This established the transportability of the delta30 mutation and its attenuation phenotype to a dengue virus type other than DEN4.  The effective transferability of the delta30 mutation establishes the usefulness of the delta30 mutation to attenuate and improve the safety of commercializable dengue virus vaccines of any serotype. 

A tetravalent dengue virus vaccine containing dengue virus types 1, 2, 3, and 4 each attenuated by the delta30 mutation is being developed.  The presence of the delta30 attenuating mutation in each virus component precludes the reversion to a wild-type virus by intertypic recombination.  In addition, because of the inherent genetic stability of deletion mutations, the delta30 mutation represents an excellent alternative for use as a common mutation shared among each component of a tetravalent vaccine.]]></description><link>http://www.ott.nih.gov/Technologies/abstractDetails.aspx?RefNo=671</link><pubDate>2011-02-28</pubDate></item><item><title>Development of Mutations Useful for Attenuating Dengue Viruses and Chimeric Dengue Viruses</title><description><![CDATA[Although flaviviruses cause a great deal of human suffering and economic loss, there is a shortage of effective vaccines.  This invention relates to dengue virus mutations that may contribute to the development of improved dengue vaccines.  Site directed and random mutagenesis techniques were used to introduce mutations into the dengue virus genome and to assemble a collection of useful mutations for incorporation in recombinant live attenuated dengue virus vaccines.  The resulting mutant viruses were screened for several valuable phenotypes, including temperature sensitivity in Vero cells or human liver cells, host cell restriction in mosquito cells or human liver cells, host cell adaptation for improved replication in Vero cells, and attenuation in mice or in mosquitoes.  The genetic basis for each observed phenotype was determined by direct sequence analysis of the genome of the mutant virus.  Mutations identified through these sequencing efforts have been further evaluated by re-introduction of the identified mutations, singly, or in combination, into recombinant dengue virus and characterization of the resulting recombinant virus for phenotypes.  In this manner, a menu of attenuating and growth promoting mutations was developed that is useful in fine-tuning the attenuation and growth characteristics of dengue virus vaccine candidates.  The mutations promoting growth in Vero cells have usefulness for the production of live or inactivated dengue virus vaccines.]]></description><link>http://www.ott.nih.gov/Technologies/abstractDetails.aspx?RefNo=535</link><pubDate>2011-02-28</pubDate></item><item><title>Compounds That Treat Malaria and Prevent Malaria Transmission</title><description><![CDATA[The invention offered for licensing relates to therapeutic compounds and related pharmaceutical compositions that can be used in the prevention and treatment of malaria infection. More specifically, the invention is drawn to compounds that can kill malaria gametocytes to block malaria transmission and treat malaria infection in the non-erthtrocytic stages, as well as therapeutic uses of these molecules to prevent or slow the transmission of plasmodium organisms between mammals and eliminate or prevent infection in mammal. Furthermore, the compounds of the invention are tricyclic compounds where the side rings may be 5-7 membered rings (preferably 6-membered), and the center ring may be 6-8 membered ring (preferably 7-membered). Also, preferable structures are ones in which the side rings are aryl rings while the center ring is cycloalkyl ring. The compounds of the invention have been identified by integrating quantitative high-throughput screening (qHTS) with genetic mapping and in vivo oocyst formation assay.]]></description><link>http://www.ott.nih.gov/Technologies/abstractDetails.aspx?RefNo=2201</link><pubDate>2011-02-28</pubDate></item><item><title>Treatment of Schistosomiasis Using Substituted Oxadiazole 2-Oxides</title><description><![CDATA[Available for licensing and commercial development are pharmaceutical compositions and methods for the treatment of Schistosomiasis in mammals.  The various compositions are based on a number of compounds derived from 1,2,5-oxadiazole that are potent inhibitors of thioredoxin glutathione reductase (TGR), a critical parasite redox protein. 

Schistosomiasis is a chronic disease caused by trematode flatworms of the genus Schistosoma, including S. mansoni, S. japonicum and S. haematobium.  Adult schistosome parasites live in an aerobic environment within human hosts, and therefore must have effective mechanisms to maintain cellular redox balance.  Additionally, the worms must be able to evade reactive oxygen species generated by the host's immune response.  In most eukaryotes there are two major systems to detoxify reactive oxygen species, one based on the tripeptide glutathione and the other based on the protein thioredoxin.  Glutathione reductase (GR) reduces glutathione disulfide, whereas thioredoxin reductases (TrxR) are pivotal in the Trx-dependent system. It was recently discovered that specialized TrxR and GR enzymes are absent in schistosomes.  Instead, they are replaced by the unique multifunctional enzyme TGR.  This reliance on a single enzyme for both glutathione disulfide and thioredoxin reduction suggests that the parasite's redox systems are subject to a bottleneck dependence on TGR, and that TGR represents a potentially important drug target. 

Schistosomiasis remains a major and neglected health problem in many tropical areas.  The health burden resulting from Schistosomiasis is estimated to include more than 200 million people infected, 779 million at risk of infection, 280,000 deaths annually, and more than 20 million individuals experiencing high morbidity.  Clinical manifestations of schistosomiasis infection include abdominal pain, cough, diarrhea, eosinophilia, fever, fatigue, and hepatosplenomegaly.  The primary route of infection occurs through contact with infected river and lake water, at which time the parasite burrows into the skin, matures, then migrates to other areas of the body.  Adult schistosome parasites reside in the mesenteric veins of their human hosts, where they can survive for up to 30 years.  The need to control schistosomiasis is acute and efforts have been ongoing for years on three main fronts:  prevention (via establishment and maintenance of sources of safe potable water), development of a vaccine, and use of drugs to treat the infection.]]></description><link>http://www.ott.nih.gov/Technologies/abstractDetails.aspx?RefNo=1902</link><pubDate>2009-03-23</pubDate></item></channel></rss>